title: Molecular evolutionary mechanisms driving functional diversification of the HSP90A family of heat shock proteins in eukaryotes.
abstract: The ubiquitous and conserved cytosolic heat-shock proteins 90 (HSP90A) perform essential functions in the cell. To understand the evolutionary origin of HSP90A functional diversification, we analyzed the distribution of HSP90A family from 54 species representing the main eukaryotic lineages. Three independent HSP90A duplications led to the paralog subfamilies HSP90AA (heat-stress inducible) and HSP90AB (constitutive) and trace back to key time points during vertebrate, seed plant, and yeast evolution. HSP90AA and HSP90AB present divergent selection pressures, positive selection (PS), and signatures of functional divergence (FD) after duplication. The differential evolutionary patterns support different mechanisms for HSP90A functional diversification in vertebrates and seed plants. Mapping of PS and FD residues onto the HSP90A structure suggests the acquisition of novel and/or specialized client protein and/or cochaperone binding functions. We propose these residues as targets for further experimental studies of HSP90A proteins, reported to be capacitors of rapid evolutionary change, and targets for anticancer therapeutics.
authors.affiliation: Institute for Plant Molecular and Cell Biology - IBMCP (CSIC-UPV), Integrative Systems Biology Group, Valencia, Spain. lorenzoc@buffalo.edu
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Carretero-Paulet
authors.forename: Victor A
authors.initials: VA
authors.lastname: Albert
authors.forename: Mario A
authors.initials: MA
authors.lastname: Fares
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D019143:Evolution, Molecular; D020440:Gene Duplication; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D008958:Models, Molecular; D010802:Phylogeny; D010944:Plants / Q000378:metabolism; D012639:Seeds / Q000378:metabolism; D012641:Selection, Genetic; D014714:Vertebrates / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins
keywords: divergent selection pressures; functional specialization; gene duplication; heat shock proteins; positive selection